Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000618410 | SCV000739935 | uncertain significance | Cardiovascular phenotype | 2016-03-03 | criteria provided, single submitter | clinical testing | The p.H1524P variant (also known as c.4571A>C), located in coding exon 31 of the MYH7 gene, results from an A to C substitution at nucleotide position 4571. The histidine at codon 1524 is replaced by proline, an amino acid with some similar properties. This variant was previously reported in the SNPDatabase as rs767148171. Based on data from ExAC, the C allele was reported in 2 of 121376 (0.002%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed February 12, 2016]). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001797112 | SCV002038713 | uncertain significance | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#520270; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27535533) |
| Invitae | RCV001868134 | SCV002298313 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-20 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 520270). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs767148171, gnomAD 0.002%). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1524 of the MYH7 protein (p.His1524Pro). |